Intestinal bile acid reabsorption in health and disease

    Research output: ThesisThesis fully internal (DIV)

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    Abstract

    Bile acids are produced by the liver and excreted in the intestine to aid the absorption of fat and fat soluble vitamins. Bile acids are reabsorbed at the end of the small intestine and reused by the liver. Recently, several new functions of bile acids have been discovered, including effects on gut health, hormones and energy metabolism. These functions have consequences for various disease conditions but also offer potential for development of new therapies.
    In this thesis we investigated the consequences of reabsorption of bile acids in both health and disease. In this regard, we studied cystic fibrosis (CF), a genetic disease leading to formation of thick mucus in various organs including the lung, liver and intestine. CF patients have reduced ability to reabsorb bile acids. The exact cause, consequences and clinical implications of this problem are unknown. Based on assessment of current literature we found a potential relation of the malabsorption of bile acids in CF to other symptoms of CF. We show that treatment of CF patients with a drug directly targeting the defective CF protein, improves their bile acid reabsorption. In a pre-clinical setting bile acid reabsorption in CF could be improved using a commonly prescribed laxative.
    Conversely, we studied the induction of bile acid malabsorption by blocking the main uptake transport protein in the intestine as a strategy to treat different metabolic conditions. We found that inducing malabsorption of bile acids prevented obesity, non-alcoholic fatty liver disease and hypercholesterolemia.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Jonker, Hans, Supervisor
    • Verkade, Henkjan, Supervisor
    • Bodewes, Frank, Co-supervisor
    Award date12-Jun-2019
    Place of Publication[Groningen]
    Publisher
    Print ISBNs978-94-034-1744-8
    Electronic ISBNs978-94-034-1743-1
    Publication statusPublished - 2019

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